Year: 2023
Type: article
Abstract: Tet2 is a member of the Ten-eleven translocation (Tet1/2/3) family of enzymes and is expressed in embryonic stem cells (ESCs). It demethylates DNA (catalytic functions) and partners with chromatin modifiers (noncatalytic functions) to regulate genes. However, the significance of these functions in ESCs is less defined. Using Tet2 catalytic mutant ( Tet2 m/m ) and knockout ( Tet2 −/− ) ESCs, we identified Tet2 target genes regulated by its catalytic dependent versus independent roles. Tet2 was enriched at their active enhancers and promoters to demethylate them. We also identified the histone deacetylase component Sin3a as a Tet2 partner, co-localizing at promoters and active enhancers. Tet2 deficiency diminished Sin3a at these regions. Tet2 and Sin3a co-occupancy overlapped with Tet1. Combined loss of Tet1/2, but not of their catalytic activities, reduced Sin3a at active enhancers. These findings establish Tet2 catalytic and noncatalytic functions as regulators of DNA demethylation and Sin3a recruitment at active enhancers in ESCs.
Source: iScience
Institution: Albert Einstein College of Medicine
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $3,150
Funders: Merck, New York State Department of Health, American Foundation for Aging Research, New York State Stem Cell Science, Relay Therapeutics, National Institutes of Health, National Heart, Lung, and Blood Institute, NIH Office of the Director, National Cancer Institute, National Institute of General Medical Sciences
OpenAlex ID: W4381051218